Piquer Sandra, Barceló-Batllori Sílvia, Julià Marta, Marzo Nuria, Nadal Belen, Guinovart Joan J, Gomis Ramon
Endocrinology and Diabetes Unit, Department of Medicine, Hospital Clínic/IDIBAPS, University of Barcelona, Barcelona, Spain.
Biochem Biophys Res Commun. 2007 Jun 29;358(2):385-91. doi: 10.1016/j.bbrc.2007.04.143. Epub 2007 Apr 30.
Oral administration of sodium tungstate is an effective treatment for diabetes in animal models. Several lines of evidence indicate the pancreatic beta cell as one of the targets of tungstate action. Here, we examined the molecular mechanism by which this compound exerts its effects on the beta cell line MIN6. Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. Although no effect was observed in glucose-induced insulin secretion we found that tungstate activates basal insulin release, a process driven, at least in part, by activation of p38. These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell.
口服钨酸钠对动物模型糖尿病是一种有效的治疗方法。多条证据表明胰腺β细胞是钨酸盐作用的靶点之一。在此，我们研究了该化合物对β细胞系MIN6发挥作用的分子机制。钨酸盐处理诱导p38和PI3K的磷酸化及随后的激活，这反过来又与钨酸盐诱导的胰腺十二指肠同源盒-1（PDX-1）核定位和激活有关。虽然在葡萄糖诱导的胰岛素分泌方面未观察到影响，但我们发现钨酸盐激活基础胰岛素释放，这一过程至少部分是由p38的激活驱动的。这些结果表明p38和PI3K磷酸化直接参与了钨酸盐在β细胞中的作用机制。
